Accurate and reproducible temperature control is required for a large number of applications in biological and chemical analysis. Such temperature control may require either a stable constant temperature over a definite time period or a temperature that varies in a predetermined manner during the overall analytical process. In general, techniques for molecular separation often benefit from temperature control. Biochemical and biophysical reactions occurring in connection with cellular assays and assays for blood chemistry and immunology also frequently involve steps that require controlled temperature.
Capillary electrophoresis is recognized as a powerful technique that can separate molecules based on size and/or charge and is one analysis technique that increasingly requires such accurate and reproducible temperature control. For example, certain applications for molecular separation by capillary electrophoresis depend on maintaining constant temperature over a predetermined length of the capillary. Such applications include DNA sequencing and constant denaturant capillary electrophoresis. Other applications rely on increasing or decreasing the temperature over a predetermined length of the capillary in accordance with a predefined temperature profile (i.e. temperature gradient capillary electrophoresis and cycling temperature capillary electrophoresis).
Recent work in the area of capillary electrophoresis has given rise to a method for periodically varying the temperature of an air oven to conduct mutation analysis in a modified DNA sequencer. However, such processes are often difficult to control in a conventional air oven. By using the air oven to control the temperature of a substance passing through a capillary column, the periodicity and amplitude of the temperature cycles are highly dependent on the overall volume of the oven chamber and the typically large combined heat capacity of everything in it. Rapid and accurate temperature control is virtually impossible to achieve. Relatively complex electromechanical configurations are also required to achieve even a minimal degree of temperature control.
In U.S. patent application Ser. No. 09/979,622, filed on Mar. 7, 2000, Foret et al. describe an apparatus that may be used to control the temperature of a substance passing through a capillary column. As shown in FIG. 2 of that application, the apparatus includes a heater body that is constructed as a cylindrical volume of thermally conductive material. The heater body is completely surrounded by an electrically powered heating element that, in turn, is completely surrounded by a cylinder constructed from a thermally insulating material. The thermally conductive material has a hole drilled through its length. A stainless steel tube is inserted through this hole and is permanently embedded within the thermally conductive material using thermal epoxy. The capillary, carrying a gel matrix through which the sample is to travel, is passed through this stainless steel tube. A plurality of these structures are combined to form a capillary array. Each individual capillary column of the capillary array is thermally insulated from every other individual capillary column.
A stated application of the Foret et. al. apparatus is constant denaturant capillary electrophoresis (CDCE). However, the present inventors have recognized several disadvantages inherent in the design of this apparatus that can make it unsuitable for CDCE applications (as well as other temperature dependent analytical processes) on a large commercial scale. For example, it is difficult to efficiently and economically incorporate the apparatus into existing analyzer designs. Generally speaking, the apparatus can also be difficult to manufacture and use due to its complex design. In addition, the temperature of the apparatus is difficult to accurately reset to an initial target temperature. Further, the overall concentric construction of the apparatus is designed to maintain long-term temperature stability at the expense of speed in achieving a target temperature. This may make the apparatus difficult to use in processes requiring a rapidly varying temperature profile.